The album's lyrical topics are darker than the lyrical topics on All Killer No Filler.[19] Sum 41's vocalist Deryck Whibley said "A lot of stuff happened in the past year that opened our eyes to new things," Whibley said. "The whole last year has been really crazy around the world. There's been so much stuff going on and it's been so televised. I think we've all become more aware. When we were writing the last record everything was happy go lucky. Now this time we've seen a little bit more and our eyes have been opened up a little bit."[10] The album's lyrical topics include hatred, war, internal demons, disliking the world, suicide, drugs, insomnia, and HIV.[10][20][19][12][21] The song "Mr. Amsterdam" is about an embittered man. Deryck Whibley said "'Mr. Amsterdam' is sort of about a guy who hates everything, very bitter person who kind of hates the world," he explains. "He's against the world."[17] The song also is about the complacency of pop culture that was contemporary in 2002, the year that Does This Look Infected? was released in, and technology that was really new during the year that the album was released in.[10] Deryck Whibley explained the meaning of "Mr. Amsterdam" saying "We depend so much on new technology to make sure that we don't have to do anything," Whibley said. "Everything's being laid out so we can sit at home and do nothing and never leave our homes. You can order all your groceries from the computer. You can do anything you want. You can just sit there and become fatter. And I think that's bad."[10]

Dave Baksh, a member of Sum 41, explained the meaning of the song "All Messed Up", saying "There's a song called 'All Messed Up,' which is about doing drugs . . . just what we feel when we're on drugs."[20] When Deryck Whibley spoke about what "All Messed Up" is about, he said "It's about those kinds of nights," Whibley said. "It's just about being really messed up and in that whole cracked-out kind of state."[10] "The Hell Song" is about a friend of Sum 41 who contracted HIV. Deryck Whibley spoke about "The Hell Song" saying "It’s one of my favorite songs on the record," Whibley said. "It's about this girl I used to date who I've known forever. Just last Christmas she found that she was HIV positive, and it was so brutal. She doesn't sleep around. She's only had two or three boyfriends and one of them used to cheat on her all the time, and then he got it and gave it to her. It's the heaviest thing that's happened in our group of friends."[10] "No Brains" is about a former band member of Sum 41. Deryck Whibley explained the song's meaning saying "That's just a basic 'fuck you, I'm done' kind of song," Whibley said. "This guy was our old singer and I was best friends with him. We had this big falling out."[10] Deryck Whibley spoke about what the song "Over My Head (Better Off Dead)" is about; he said "It's not about being fucked up or drunk," Whibley said. "It's more about the aftermath when you're hearing everything you've just done the night before, and you're like, "Ah, fuck, I'm better off dead." I don't regret any of the things I do and I don't mind doing them, I just hate hearing about it. Being told every morning, "Dude, what did you do last night?" drives me nuts."[10]

"Still Waiting" was written after the attacks that occurred on September 11, 2001.[10] Deryck Whibley explained the meaning of the song saying "It's not directly about 9/11 or the war on terrorism," he said. "It's about the war on everything. It's about the world as we know it. It's no secret that the world doesn't get along and there's all this hatred. It's everything to do with how this world functions."[10] Sum 41's vocalist Deryck Whibley stated on the band's DVD Sake Bombs And Happy Endings that the album's song "A.N.I.C." is a "special love song" dedicated to Anna Nicole Smith. According to him, "A.N.I.C." stands for "Anna Nicole is a Cunt". Sum 41 member Dave Baksh said that Anna Nicole Smith is "a fuckin' loser" and also said "Look what she's doing to herself."[20] Sum 41 stopped including the song in their live performances after Anna Nicole Smith died of an overdose in 2007.[22] However, they put "A.N.I.C." back to their setlist during the 2012 summer European leg of the Screaming Bloody Murder Tour, However, when Sum 41 would perform the song live after Anna Nicole Smith's death, the band wouldn't show any disrespect towards Anna Nicole Smith, with Deryck Whibley saying that the song "A.N.I.C." stands for "Deryck Whibley is a Stupid Fucking Cunt".

The cover for Does This Look Infected? features drummer Steve Jocz dressed up as a zombie. It was chosen months before the title was. The album was almost delayed by the label because the band members did not have a name for it on time until Whibley thought of the name Does This Look Infected?. The whole band laughed at the idea and chose it as their album title. The same thing is also used on the band's EP Does This Look Infected Too?, except Jocz was replaced with Whibley, also dressed as a zombie.

Does This Look Infected? has received positive reviews from music critics. On Metacritic, the album has a 75 out of 100. E! Online said that it "has a clutch of songs that mix chord-y abandon with raging rock riffs--and a heck of a lot of good times." Blender also gave it a positive review, saying "So Sum 41 have grown up... a little.... It's all relative, and, crucially, it still rocks." The album has been acclaimed by the fanbase, and has been considered a fan favorite. The album was included at number 28 on Rock Sound's "The 51 Most Essential Pop Punk Albums of All Time" list.[25]

The album gained commercial success, with singles "The Hell Song" and "Still Waiting" mainly gaining success on the modern rock charts. The album has sold over 860,000 copies worldwide, but the album didn't gain quite as much success as the band's previous album "All Killer No Filler".

The unedited version includes a bonus DVD which is entitled Cross The T's and Gouge Your I's. The DVD has footage of Sum 41's alter ego band, Pain for Pleasure, titled "Reign In Pain", as well as various humorous segments like "Going Going Gonorrhea", "Campus Invasion", and "Pizza Heist and Other Crap". Also included in the DVD are the Pain for Pleasure tracks "Reign In Pain" and "WWVII Parts 1 & 2", the Autopilot Off songs "Long Way to Fall" and "Nothing Frequency", the No Warning songs "Short Fuse" and "Ill Blood", and some web-links.